1. Technical Field
The present invention relates generally to lyophilization and more particularly, to a wireless temperature sensing system for lyophilization processes.
2. Related Art
Freeze-drying is a technique by which water is removed from a frozen system through a process of sublimation. Sublimation is the process by which, at low temperatures and pressures, water is removed from a frozen system by going directly from a solid to a gas, thereby skipping the liquid phase. This process allows physical structure, established during freezing, to be maintained in the dried state.
After sublimation, the evolved water vapor migrates to a condenser where it freezes and collects. Skipping the solution phase through sublimation allows certain compounds, which are not stable for extended periods of time in solution, to be stabilized by placing them in a state of “suspended animation” within the dried solid. At the time of use, the dried product is returned to its original solution state by adding sterile water and mixing. It is of particular importance to monitor product temperature during freeze-drying as the product can be destroyed if it is not held at the appropriate temperature.
The current technique for measuring product temperature is by placing thermocouples directly in the product. These thermocouples are composed of two different wires (typically containing copper and constantan, respectively) that are welded at the tip. The welded end of the wire is placed in the solution contained in the vials, and the other end plugs into a socket in the freeze-dryer chamber which feeds information to a computer. The thermocouple is essentially a circuit that is formed by joining the ends of two wires from different metals, and the junction is exposed to different temperatures. An electrical potential (emf) develops between the two wires that is directly related to the temperature difference, and the current flow in the circuit.
Many problems are encountered with conventional thermocouples. The wires running from the vials to the sockets in the chamber regularly knock other vials over spilling liquids on the shelf. Additionally, adding thermocouples and plugging them in by an operator in an aseptic environment has the potential to contaminate other samples within the batch. Removing the wired connection between the vial and socket would greatly reduce the aforementioned problems. Additionally, large-scale pharmaceutical freeze-drying technology is currently moving towards complete process automation including automatic loading and unloading of the vials from the dryer. This automated process makes product temperature monitoring via conventional thermocouples impossible and valuable product temperature information is lost.
As a result of the aforementioned problems, a need exists for a method and system of monitoring the temperature of product during the freeze-drying process that does not require operator intervention into the freeze-drying chamber and may be readily adapted for automatic loading and unloading of the vials.